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Journal of Neuroscience, Vol 13, 2829-2836, Copyright © 1993 by Society for Neuroscience
Glutamate neurons in hypothalamus regulate excitatory transmission
AN van den Pol and PQ Trombley
Section of Neurosurgery, Yale University Medical School, New Haven, Connecticut 06510.
The hypothalamus is the crucial part of the brain that regulates
homeostasis throughout the body. It governs the endocrine and autonomic
nervous systems, temperature, heart rate, emotional and motivational
states, reproduction, energy and water balances, and circadian rhythms. In
contrast to the prevailing belief that hypothalamic neurons use peptides,
neuromodulators, or other slow-acting agents as their principal neuroactive
substances, we present data indicating that the primary excitatory
transmitter released by medial hypothalamic neurons is glutamate. This
surprising new evidence is based on three converging approaches: Immunogold
cytochemistry revealed that some hypothalamic neurons and their processes
in vitro contained high amounts of immunoreactive glutamate. Ca2+ digital
video imaging showed that cytoplasmic Ca2+ levels of cultured neurons,
elevated because of spontaneous presynaptic release of a hypothalamic
transmitter, were reduced by perfusion with the selective glutamate
receptor antagonists cyano-2,3-dihydroxy-7-nitroquinoxaline and
2-aminophosphonovaleric acid. Electrophysiological analysis of whole-cell
patch-clamp recordings from single and pairs of monosynaptically coupled
hypothalamic neurons in culture showed that virtually all spontaneous and
evoked EPSPs appear to be mediated by synaptic secretion of glutamate.
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